Hypothalamic actions of neuromedin U.

The central nervous system and gut peptide neuromedin U (NMU) inhibits feeding after intracerebroventricular injection. This study explored the hypothalamic actions of NMU on feeding and the hypothalamo-pituitary-adrenal axis. Intraparaventricular nucleus (intra-PVN) NMU dose-dependently inhibited food intake, with a minimum effective dose of 0.1 nmol and a robust effect at 0.3 nmol. Feeding inhibition was mapped by NMU injection into eight hypothalamic areas. NMU (0.3 nmol) inhibited food intake in the PVN (0-1 h, 59 ± 6.9% of the control value; P < 0.001) and arcuate nucleus (0-1 h, 76 ± 10.4% of the control value; P < 0.05). Intra-PVN NMU markedly increased grooming and locomotor behavior and dose-dependently increased plasma ACTH (0.3 nmol NMU, 24.8 ± 1.9 pg/ml; saline, 11.4 ± 1.0; P < 0.001) and corticosterone (0.3 nmol NMU, 275.4 ± 40.5 ng/ml; saline, 129.4 ± 25.0; P < 0.01). Using hypothalamic explants in vitro, NMU stimulated CRH (100 nM NMU, 5.9 ± 0.95 pmol/explant; basal, 3.8 ± 0.39; P < 0.01) and arginine vasopressin release (100 nM NMU, 124.5 ± 21.8 fmol/explant; basal, 74.5 ± 7.6; P < 0.01). Leptin stimulated NMU release (141.9 ± 20.4 fmol/explant; basal, 92.9 ± 9.4; P < 0.01). Thus, we describe a novel role for NMU in the PVN to stimulate the hypothalamo-pituitary-adrenal axis and locomotor and grooming behavior and to inhibit feeding

ICAR: endoscopic skull‐base surgery

n/

The response of relativistic outflowing gas to the inner accretion disk of a black hole

The brightness of an active galactic nucleus is set by the gas falling onto it from the galaxy, and the gas infall rate is regulated by the brightness of the active galactic nucleus; this feedback loop is the process by which supermassive black holes in the centres of galaxies may moderate the growth of their hosts. Gas outflows (in the form of disk winds) release huge quantities of energy into the interstellar medium, potentially clearing the surrounding gas. The most extreme (in terms of speed and energy) of these-the ultrafast outflows-are the subset of X-ray-detected outflows with velocities higher than 10,000 kilometres per second, believed to originate in relativistic (that is, near the speed of light) disk winds a few hundred gravitational radii from the black hole. The absorption features produced by these outflows are variable, but no clear link has been found between the behaviour of the X-ray continuum and the velocity or optical depth of the outflows, owing to the long timescales of quasar variability. Here we report the observation of multiple absorption lines from an extreme ultrafast gas flow in the X-ray spectrum of the active galactic nucleus IRAS 13224-3809, at 0.236 ± 0.006 times the speed of light (71,000 kilometres per second), where the absorption is strongly anti-correlated with the emission of X-rays from the inner regions of the accretion disk. If the gas flow is identified as a genuine outflow then it is in the fastest five per cent of such winds, and its variability is hundreds of times faster than in other variable winds, allowing us to observe in hours what would take months in a quasar. We find X-ray spectral signatures of the wind simultaneously in both low- and high-energy detectors, suggesting a single ionized outflow, linking the low- and high-energy absorption lines. That this disk wind is responding to the emission from the inner accretion disk demonstrates a connection between accretion processes occurring on very different scales: the X-ray emission from within a few gravitational radii of the black hole ionizing the disk wind hundreds of gravitational radii further away as the X-ray flux rises.M.L.P., C.P., A.C.F. and A.L. acknowledge support from the European Research Council through Advanced Grant on Feedback 340492. W.N.A. and G.M. acknowledge support from the European Union Seventh Framework Programme (FP7/2013-2017) under grant agreement number 312789, StrongGravity. D.J.K.B. acknowledges support from the Science and Technology Facilities Council. This work is based on observations with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA. D.R.W. is supported by NASA through Einstein Postdoctoral Fellowship grant number PF6-170160, awarded by the Chandra X-ray Center, operated by the Smithsonian Astrophysical Observatory for NASA under contract NAS8-03060. This work made use of data from the NuSTAR mission, a project led by the California Institute of Technology, managed by the Jet Propulsion Laboratory, and funded by NASA. This research has made use of the NuSTAR Data Analysis Software (NuSTARDAS) jointly developed by the ASI Science Data Center and the California Institute of Technology